Imidazoles, as a class, enjoy a reputation as antifungal agents. See L. Tanenbaum, et al, Archives of Dermatology -- Vol. 120, (1984) pages 216-19, which reports a study of the effects of sulconazole and miconazole creams on Tinea Versicolor. See also S. A. Qadripur, Curr. Therapeutic Res., Vol. 35, No. 5, (1984), pages 753-8. There, the research found that the use of sulconazole 1% cream along with sulconazole powder performed about as well as econazole 1% cream and powder in treating cutaneous dermatophytoses.
Among the imidazoles, compounds of formula I ##STR1## wherein X =O or S and n =1, 2 or 3, and their pharmaceutically acceptable derivatives, e.g. nitrate salts, have achieved a certain prominence where antifungal indications are concerned.
In a study of sulconazole nitrate cream versus clotrimazole cream for treating dermatophytoses, the sulconazole treated group showed faster systematic improvement. A. Lassus, et al British Journal of Dermatology, 108, (1983) pages 195-8.
In treating cutaneous candidiasis, sulconazole nitrate cream outperformed both its vehicle and miconazole nitrate cream. L. Tannebaum, et al, Int'l. Jour. of Dermatology, 22, (June, 1983), pages 318-20.
When compared to econazole in the treatment of dermatophytosis, sulconazole gave faster and more complete relief to patients. A. Lassus, et al, Mykosen 27, Heft. 12, (1984), pages 594-98.
The use of imidazoles in combination with steroids to treat fungal infections is well known. It is believed that the steroids work during the first few days of treatment to quiet inflammation, while the imidazoles work in several (i.e., generally 3 to 5) weeks to eliminate the fungal agent(s).
British specification 1474510 (published May 25, 1977,) describes ointments containing both imidazoles (as antifungals) and steroids (as anti-inflammatories). Likewise, U.S. Pat. No. 4,298,604 deals with antifungal formulations which contain clotrimazole and betamethasone dipropionate.
U.S. Pat. No. 5,002,938 discloses topical antifungal gels containing imidazoles and 17-ester corticosteroids useful for treating fungal infections.
Interestingly, the use of imidazoles alone to treat inflammations has not been directly studied. There have, however, been reports of work on the immunologic effects of a few imidazoles.
E. Drouket, et al, in Zentrobl, Baktenol, Mikrobiol Hyg., Suppl. 13, (1985) pages 1-37 disclosed that ketoconazole is an immunomodulating drug, with responses being dose dependent. Miconazole was shown to have a suppressive effect on delayed type hypersensitivity, so that it may be of use in transplantation cases.
Also, K. Watanabe, et al, reported in Pharmacometrics (Japan), vol. 29, No. 4 (1985), pages 501-15, the immune, phototoxic and photoallergenic responses of guinea pigs to sulconazole administered in various forms.
The enzymes, 5-lipoxygenase and cyclooxygenase, catalyze the formation of leukotrienes which are important mediators of inflammation. D. Steinhilber et al, in Arzneim.-Forsch./Drug Res., vol. 40, No. 11 (1990), pages 1260-1263 reported that itraconazole, inhibited 5-lipoxygenase but not cycloxygenase, in an in vitro cell culture experime,nt. However, none of the other azoles tested, i.e., fluconazole, ketokonazole and miconazole, were significantly active in this model.
All disclosures referred to herein are hereby incorporated by reference.